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BMJ Open Jul 2024Critically ill patients are at risk of suboptimal beta-lactam antibiotic (beta-lactam) exposure due to the impact of altered physiology on pharmacokinetics. Suboptimal...
INTRODUCTION
Critically ill patients are at risk of suboptimal beta-lactam antibiotic (beta-lactam) exposure due to the impact of altered physiology on pharmacokinetics. Suboptimal concentrations can lead to treatment failure or toxicity. Therapeutic drug monitoring (TDM) involves adjusting doses based on measured plasma concentrations and individualising dosing to improve the likelihood of improving exposure. Despite its potential benefits, its adoption has been slow, and data on implementation, dose adaptation and safety are sparse. The aim of this trial is to assess the feasibility and fidelity of implementing beta-lactam TDM-guided dosing in the intensive care unit setting.
METHODS AND ANALYSIS
A beta-lactam antibiotic Dose AdaPtation feasibility randomised controlled Trial using Therapeutic Drug Monitoring (ADAPT-TDM) is a single-centre, unblinded, feasibility randomised controlled trial aiming to enroll up to 60 critically ill adult participants (≥18 years). TDM and dose adjustment will be performed daily in the intervention group; the standard of care group will undergo plasma sampling, but no dose adjustment. The main outcomes include: (1) feasibility of recruitment, defined as the number of participants who are recruited from a pool of eligible participants, and (2) fidelity of TDM, defined as the degree to which TDM as a test is delivered as intended, from accurate sample collection, sample processing to result availability. Secondary outcomes include target attainment, uptake of TDM-guided dosing and incidence of neurotoxicity, hepatotoxicity and nephrotoxicity.
ETHICS AND DISSEMINATION
This study has been approved by the Alfred Hospital human research ethics committee, Office of Ethics and Research Governance (reference: Project No. 565/22; date of approval: 22/11/2022). Prospective consent will be obtained and the study will be conducted in accordance with the Declaration of Helsinki. The finalised manuscript, including aggregate data, will be submitted for publication in a peer reviewed journal. ADAPT-TDM will determine whether beta-lactam TDM-guided dose adaptation is reproducible and feasible and provide important information required to implement this intervention in a phase III trial.
TRIAL REGISTRATION NUMBER
Australian New Zealand Clinical Trials Registry, ACTRN12623000032651.
Topics: Humans; Drug Monitoring; Anti-Bacterial Agents; Feasibility Studies; Critical Illness; beta-Lactams; Randomized Controlled Trials as Topic; Intensive Care Units
PubMed: 38951004
DOI: 10.1136/bmjopen-2023-083635 -
PloS One 2024Electrospun (ES) fibrous nanomaterials have been widely investigated as novel biomaterials. These biomaterials have to be safe and biocompatible; hence, they need to be...
Electrospun (ES) fibrous nanomaterials have been widely investigated as novel biomaterials. These biomaterials have to be safe and biocompatible; hence, they need to be tested for cytotoxicity before being administered to patients. The aim of this study was to develop a suitable and biorelevant in vitro cytotoxicity assay for ES biomaterials (e.g. wound dressings). We compared different in vitro cytotoxicity assays, and our model wound dressing was made from polycaprolactone and polyethylene oxide and contained chloramphenicol as the active pharmaceutical ingredient. Baby Hamster Kidney cells (BHK-21), human primary fibroblasts and MTS assays together with real-time cell analysis were selected. The extract exposure and direct contact safety evaluation setups were tested together with microscopic techniques. We found that while extract exposure assays are suitable for the initial testing, the biocompatibility of the biomaterial is revealed in in vitro direct contact assays where cell interactions with the ES wound dressing are evaluated. We observed significant differences in the experimental outcome, caused by the experimental set up modification such as cell line choice, cell medium and controls used, conducting the phosphate buffer washing step or not. A more detailed technical protocol for the in vitro cytotoxicity assessment of ES wound dressings was developed.
Topics: Animals; Wound Healing; Biocompatible Materials; Humans; Bandages; Cell Line; Materials Testing; Cricetinae; Polyesters; Fibroblasts; Anti-Infective Agents; Polyethylene Glycols; Chloramphenicol
PubMed: 38950036
DOI: 10.1371/journal.pone.0305137 -
Dental and Medical Problems 2024Despite the superiority of glass-ionomer cements (GICs) over composites in treating white spot lesions (WSLs), there is still a concern about their preventive and...
BACKGROUND
Despite the superiority of glass-ionomer cements (GICs) over composites in treating white spot lesions (WSLs), there is still a concern about their preventive and antibacterial properties. Efforts have been made to improve the strength of their bond to demineralized enamel, fluoride release and antibacterial properties by adding nanoparticles of chitosan, which seems to be a promising method.
OBJECTIVES
The aim of the present study was to assess the antibacterial effect, the microshear bond strength (μSBS) to enamel at the WSL area, and the fluoride and nano-chitosan release after modifying the polyacrylic acid liquid phase of a traditional GIC with different nano-chitosan volumes.
MATERIAL AND METHODS
A total of 120 samples were prepared, and then divided into 4 groups (n = 30): G1 - non-modified GIC, which served as a control group, while G2, G3 and G4 were modified with different nano-chitosan volumes (50%, 100% and 150%, respectively). Microshear bond strength was assessed using a universal testing machine (UTM) after storage in distilled water for 24 h. Fluoride and nanochitosan release was measured with the use of spectrophotometers at different time points (initially, and at 1 h, 24 h, 48 h, 72 h, 1 week, 2 weeks, 3 weeks, and 6 weeks) after storage in distilled water. The antibacterial effect against the Streptococcus aureus strain was assessed with the agar diffusion test. The data was statistically analyzed.
RESULTS
After 24-hour storage, G2 recorded a slight, yet non-significant, increase in the μSBS values (4.1 ±0.94 MPa) as compared to G1 (3.9 ±1.30 MPa). With regard to fluoride release, the amount recorded for G1 was significantly greater at the end of the 24-hour storage period (0.70 ±0.30 μmf/cm2) than modified nano-chitosan GIC groups; G1 was followed by G4 (0.54 ±0.34 μmf/cm2). The highest amount of nano-chitosan release after 24-hour storage was noted for G3 (0.85 ±0.00 μmf/cm2). The highest inhibition zone value was recorded for G2.
CONCLUSIONS
Glass-ionomer cement modified with 50% nano-chitosan was shown to positively affect μSBS and the antibacterial effect, while modification with 150% nano-chitosan significantly increased fluoride release.
Topics: Chitosan; Anti-Bacterial Agents; Glass Ionomer Cements; Dental Caries; In Vitro Techniques; Fluorides; Humans; Nanoparticles; Shear Strength; Dental Enamel; Materials Testing; Dental Bonding
PubMed: 38949834
DOI: 10.17219/dmp/158835 -
EuroIntervention : Journal of EuroPCR... Jul 2024
Topics: Humans; Coronary Artery Disease; Registries; Sirolimus; Treatment Outcome; Angioplasty, Balloon, Coronary; Male; Female; Middle Aged; Aged; Drug-Eluting Stents
PubMed: 38949239
DOI: 10.4244/EIJ-D-23-00966 -
JPMA. the Journal of the Pakistan... Jun 2024To determine the predisposing factors for lengthy intensive care unit stay of chronic obstructive pulmonary disease patients with acute exacerbation.
OBJECTIVES
To determine the predisposing factors for lengthy intensive care unit stay of chronic obstructive pulmonary disease patients with acute exacerbation.
METHODS
The retrospective study was conducted after approval from the ethics review committee of Atatürk Sanatorium Training and Research Hospital, Turkey, and comprised data from January 1, 2017, to August 31, 2022, related to acute exacerbation chronic obstructive pulmonary disease patients receiving intensive care unit treatment. Demographics, comorbidities, treatment, length of stay in hospital and in intensive care unit, and nutritional status were evaluated. Data of patients who spent <10 days in intensive care unit formed Group 1, while those having spent 10 days or more formed Group 2 for comparison purposes. Data was analysed using SPSS 22.
RESULTS
Of the 460 patients, 366(79.6%) were in Group 1; 224(61.2%) males and 64(38.8%) females with mean age 70.81±11.57 years. There were 94(20.4%) patients in Group 2; 62(66%) males and 32(34%) females with mean age 72.38±10.88 years (p>0.05). Inotropic agent support, need for haemodialysis, timeframe of invasive mechanical ventilation, length of stay in hospital, 1-month mortality, antibiotic use, use of diuretic agent, acute physiology and chronic health evaluation-ii score, nutrition risk in the critically ill score, history of lung malignancy, and pneumonic infiltration on chest radiograph were significantly more frequenttly observed in Group 2 patients (p<0.05). Age, timeframe of invasive mechanical ventilation, and length of stay in hospital were the factors prolonging intensive care unit stay (p<0.05).
CONCLUSIONS
Higher age, longer invasive mechanical ventilation timeframe and hospital stay with acute exacerbation chronic obstructive pulmonary disease caused a prolonged stay in intensive care unit.
Topics: Humans; Male; Pulmonary Disease, Chronic Obstructive; Female; Aged; Length of Stay; Retrospective Studies; Middle Aged; Aged, 80 and over; Risk Factors; Disease Progression; Intensive Care Units; Critical Care; Respiration, Artificial; Turkey; Nutritional Status; Anti-Bacterial Agents; Renal Dialysis
PubMed: 38948972
DOI: 10.47391/JPMA.9418 -
PeerJ 2024In the present study, zinc oxide nanoparticles (ZnO-NPs) were synthesized using neem leaf aqueous extracts and characterized using transmission electron microscopy...
In the present study, zinc oxide nanoparticles (ZnO-NPs) were synthesized using neem leaf aqueous extracts and characterized using transmission electron microscopy (TEM), ultraviolet visible spectroscopy (UV-Vis), and dynamic light scattering (DLS). Then compare its efficacy as anticancer and antibacterial agents with chemically synthesized ZnO-NPs and the neem leaf extract used for the green synthesis of ZnO-NPs. The TEM, UV-vis, and particle size confirmed that the developed ZnO-NPs are nanoscale. The chemically and greenly synthesized ZnO-NPs showed their optical absorbance at 328 nm and 380 nm, respectively, and were observed as spherical particles with a size of about 85 nm and 62.5 nm, respectively. HPLC and GC-MS were utilized to identify the bioactive components in the neem leaf aqueous extract employed for the eco-friendly production of ZnO-NPs. The HPLC analysis revealed that the aqueous extract of neem leaf contains 19 phenolic component fractions. The GC-MS analysis revealed the existence of 21 bioactive compounds. The antiproliferative effect of green ZnO-NPs was observed at different concentrations (31.25 µg/mL-1000 µg/mL) on Hct 116 and A 549 cancer cells, with an IC50 value of 111 µg/mL for A 549 and 118 µg/mL for Hct 116. On the other hand, the antibacterial activity against gram-positive and gram-negative bacteria was estimated. The antibacterial result showed that the MIC of green synthesized ZnO-NPs against gram-positive and gram-negative bacteria were 5, and 1 µg/mL. Hence, they could be utilized as effective antibacterial and antiproliferative agents.
Topics: Zinc Oxide; Anti-Bacterial Agents; Plant Extracts; Humans; Plant Leaves; Antineoplastic Agents; Azadirachta; Metal Nanoparticles; Microbial Sensitivity Tests; Green Chemistry Technology; Particle Size; Cell Line, Tumor
PubMed: 38948224
DOI: 10.7717/peerj.17588 -
Frontiers in Public Health 2024The Eastern Mediterranean Regional Office (EMRO) region accounts for almost 8% of all global (TB) cases, with TB incidence rates ranging from 1 per 100,000 per year in...
Epidemiology and antimicrobial resistance of spp. in the United Arab Emirates: a retrospective analysis of 12 years of national antimicrobial resistance surveillance data.
INTRODUCTION
The Eastern Mediterranean Regional Office (EMRO) region accounts for almost 8% of all global (TB) cases, with TB incidence rates ranging from 1 per 100,000 per year in the United Arab Emirates (UAE) to 204 per 100,000 in Djibouti. The national surveillance data from the Middle East and North Africa (MENA) region on the epidemiology and antimicrobial resistance trends of TB, including MDR-TB remains scarce.
METHODS
A retrospective 12-year analysis of = 8,086 non-duplicate diagnostic complex (MTB complex) isolates from the UAE was conducted. Data were generated through routine patient care during the 2010-2021 years, collected by trained personnel and reported by participating surveillance sites to the UAE National Antimicrobial Resistance (AMR) Surveillance program. Data analysis was conducted with WHONET, a windows-based microbiology laboratory database management software developed by the World Health Organization Collaborating Center for Surveillance of Antimicrobial Resistance, Boston, United States (https://whonet.org/).
RESULTS
A total of 8,086 MTB-complex isolates were analyzed. MTB-complex was primarily isolated from respiratory samples (sputum 80.1%, broncho-alveolar lavage 4.6%, pleural fluid 4.1%). Inpatients accounted for 63.2%, including 1.3% from ICU. Nationality was known for 84.3% of patients, including 3.8% Emiratis. Of UAE non-nationals, 80.5% were from 110 countries, most of which were Asian countries. India accounted for 20.8%, Pakistan 13.6%, Philippines 12.7%, and Bangladesh 7.8%. Rifampicin-resistant MTB-complex isolates (RR-TB) were found in 2.8% of the isolates, resistance to isoniazid, streptomycin, pyrazinamide, and ethambutol, was 8.9, 6.9, 3.4 and 0.4%, respectively. A slightly increasing trend of resistance among MTB-complex was observed for rifampicin from 2.5% (2010) to 2.8% (2021).
CONCLUSION
Infections due to MTB-complex are relatively uncommon in the United Arab Emirates compared to other countries in the MENA region. Most TB patients in the UAE are of Asian origin, mainly from countries with a high prevalence of TB. Resistance to first line anti-tuberculous drugs is generally low, however increasing trends for MDR-TB mainly rifampicin linked resistance is a major concern. MDR-TB was not associated with a higher mortality, admission to ICU, or increased length of hospitalization as compared to non-MDR-TB.
Topics: United Arab Emirates; Humans; Retrospective Studies; Tuberculosis, Multidrug-Resistant; Male; Mycobacterium tuberculosis; Female; Adult; Antitubercular Agents; Middle Aged; Drug Resistance, Bacterial; Adolescent; Microbial Sensitivity Tests; Young Adult; Population Surveillance
PubMed: 38947352
DOI: 10.3389/fpubh.2024.1244353 -
The Pan African Medical Journal 2024Epididymal tuberculosis is rare and often presents diagnostic difficulties. It may be indicative of a disseminated form of the infection, which is the case of our...
Epididymal tuberculosis is rare and often presents diagnostic difficulties. It may be indicative of a disseminated form of the infection, which is the case of our patient. A 19-year-old man, with no past medical history, was admitted for a swollen painful left scrotum that had been evolving for 8 months. He had undergone an orchiectomy and the anatomopathological examination was consistent with epididymal tuberculosis. The radiological investigations had revealed other localizations of the infection: lymphatic, pulmonary, parietal and osteoarticular tuberculosis. Anti-tuberculosis therapy was introduced. However, in the 4 month of treatment, the patient developed seizures. A cerebral magnetic resonance imaging was practiced, concluding to cerebral tuberculomas. Anti-tuberculosis treatment was continued associated to an anticonvulsant with a favourable outcome. The originality of our observation resides in the mode of revelation of a disseminated paucisymptomatic tuberculosis, by an epididymal localization, in an immunocompetent patient.
Topics: Humans; Male; Young Adult; Antitubercular Agents; Magnetic Resonance Imaging; Epididymis; Tuberculosis, Male Genital; Immunocompetence; Orchiectomy; Seizures; Anticonvulsants; Tuberculoma, Intracranial
PubMed: 38946746
DOI: 10.11604/pamj.2024.48.2.42965 -
European Review For Medical and... Jun 2024The non-invasive detection of Helicobacter pylori (H. pylori) and its resistance to clarithromycin and levofloxacin significantly improves the management of infected...
OBJECTIVE
The non-invasive detection of Helicobacter pylori (H. pylori) and its resistance to clarithromycin and levofloxacin significantly improves the management of infected patients by enabling tailored eradication treatments without the need for endoscopic procedures. This study aimed to assess the effectiveness of real-time PCR (RT-PCR) assays in identifying H. pylori infection and antibiotic resistance in stool and gastric biopsy specimens.
PATIENTS AND METHODS
Stool and gastric biopsy samples were collected from patients within three days of post-hospitalization. A total of 115 samples were analyzed for H. pylori infection, and an additional 115 samples were evaluated for resistance to clarithromycin and levofloxacin using an RT-PCR-based molecular test. Statistical analyses were performed using (SPSS 26.0 IBM Corp., Armonk, NY, USA).
RESULTS
Among 115 patients (53 males, average age 50.8±13.2 years), H. pylori was detected in 93.1% of stool samples and 93.9% of gastric biopsies. The RT-PCR assay demonstrated a sensitivity of 99.1% and a specificity of 100%, with an overall diagnostic accuracy of 99.1%. Clarithromycin resistance was found in 37.3% of stool and 46.9% of gastric biopsy specimens, with the assay showing 79.6% sensitivity and 98.4% specificity. Levofloxacin resistance was identified in 32.1% of stool samples and 31.3% of gastric biopsies, with 86.3% sensitivity and 91.1% specificity of the molecular test.
CONCLUSIONS
The RT-PCR-based detection of H. pylori and its resistance to clarithromycin and levofloxacin in stool samples represents a promising approach to enhance eradication therapy outcomes, potentially improving treatment efficacy. Chictr.org.cn: ChiCTR2300070267.
Topics: Humans; Levofloxacin; Clarithromycin; Helicobacter pylori; Feces; Male; Real-Time Polymerase Chain Reaction; Middle Aged; Female; Helicobacter Infections; Anti-Bacterial Agents; Drug Resistance, Bacterial; Adult; Aged; Microbial Sensitivity Tests
PubMed: 38946381
DOI: 10.26355/eurrev_202406_36460 -
Veterinary Medicine and Science Jul 2024Salmonellosis is one of the most common food-borne diseases in industrialised and developing countries. In recent year, an increase in antimicrobial resistance among...
BACKGROUND
Salmonellosis is one of the most common food-borne diseases in industrialised and developing countries. In recent year, an increase in antimicrobial resistance among different Salmonella serotypes has been observed.
OBJECTIVE
A cross-sectional study was conducted to assess the prevalence and antimicrobial susceptibility of Salmonella isolated from local chicken eggs in four selected towns in Ethiopia.
METHODS
A total of 115 eggs were examined to detect Salmonella by using standard microbiological methods. The susceptibilities of the isolates to nine antimicrobials were tested by the Kirby-Bauer disk diffusion method.
RESULT
The study revealed that of the 115 eggs examined, 22 (19.1%) were positive for Salmonella of which 14 (12.2%) and 8 (7%) of the isolates were from shells and contents, respectively. The occurrence of Salmonella in egg shells and content and between different altitudes did not differ significantly (p > 0.05). Most isolates were resistant to more than three antimicrobials with a high resistance to kanamycin, ampicillin, nalidixic acid, cotrimoxazole, oxytetracycline and chloramphenicol.
CONCLUSION
The results indicate the potential importance of local chicken eggs as source of multiple antimicrobial-resistant salmonellae and the need for proper cooking before consumption. Further studies are required to describe the epidemiology of Salmonella in various agroclimatic zones of Ethiopia.
Topics: Animals; Ethiopia; Chickens; Salmonella; Prevalence; Cross-Sectional Studies; Anti-Bacterial Agents; Poultry Diseases; Eggs; Drug Resistance, Bacterial; Salmonella Infections, Animal; Food Microbiology
PubMed: 38946179
DOI: 10.1002/vms3.1529